Polychlorinated biphenyls (PCBs) are widespread contaminants in both the general environment and workplace that have been demonstrated epidemiologically and experimentally to have neurotoxic properties. Enactment of the federal mandate to remove all PCBs from the workplace will further expose workers to PCBs and increases the need for sensitive, objective measures of possible neurological dysfunction. We propose to undertake a series of experiments using the laboratory rat to assess the feasibility of using peripherally obtained biological specimens such as serum and urine to estimate possible neurological dysfunction caused by acute and sub-chronic exposure to PCBs. We will assess neurological changes by simultaneously determining catechol and indoleamine (biogenic) neurotransmitters and metabolites in urine and serum using high performance liquid chromatography with electrochemical detection. More specifically, we propose to determine: the relationship between systemic exposure to both complex mixtures of PCB congeners and specific isomers and central nervous system (CNS) function as determined by changes in peripheral neurotransmitter metabolites; the relative persistence of these changes following removal from exposure; and the relative neurotoxicities of the major PCB congeners in the adult laboratory rat. These studies will permit the determination of PCB-induced changes in important CNS neurotransmitters, the relationship between central PCB levels and CNS function and the correlations between urinary and serum estimates of CNS biogenic amine metabolism and the determination of PCB congener body/brain burden ratios. These experiments will permit the validation of peripheral measures of CNS function as an objective screening instrument for the detection of PCB-induced neurotoxicity in the workplace.